Voet Arnout R D, Noguchi Hiroki, Addy Christine, Simoncini David, Terada Daiki, Unzai Satoru, Park Sam-Yong, Zhang Kam Y J, Tame Jeremy R H
Structural Bioinformatics Team, Division of Structural and Synthetic Biology, Center for Life Science Technologies, RIKEN, 1-7-22 Suehiro, Yokohama, Kanagawa 230-0045, Japan; and Drug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro, Yokohama, Kanagawa 230-0045, Japan.
Drug Design Laboratory, Graduate School of Medical Life Science, Yokohama City University, 1-7-29 Suehiro, Yokohama, Kanagawa 230-0045, Japan.
Proc Natl Acad Sci U S A. 2014 Oct 21;111(42):15102-7. doi: 10.1073/pnas.1412768111. Epub 2014 Oct 6.
The modular structure of many protein families, such as β-propeller proteins, strongly implies that duplication played an important role in their evolution, leading to highly symmetrical intermediate forms. Previous attempts to create perfectly symmetrical propeller proteins have failed, however. We have therefore developed a new and rapid computational approach to design such proteins. As a test case, we have created a sixfold symmetrical β-propeller protein and experimentally validated the structure using X-ray crystallography. Each blade consists of 42 residues. Proteins carrying 2-10 identical blades were also expressed and purified. Two or three tandem blades assemble to recreate the highly stable sixfold symmetrical architecture, consistent with the duplication and fusion theory. The other proteins produce different monodisperse complexes, up to 42 blades (180 kDa) in size, which self-assemble according to simple symmetry rules. Our procedure is suitable for creating nano-building blocks from different protein templates of desired symmetry.
许多蛋白质家族的模块化结构，如β-螺旋桨蛋白，强烈暗示着基因复制在其进化过程中发挥了重要作用，从而产生了高度对称的中间形式。然而，此前创建完美对称螺旋桨蛋白的尝试均以失败告终。因此，我们开发了一种全新的快速计算方法来设计此类蛋白质。作为一个测试案例，我们创建了一种六重对称的β-螺旋桨蛋白，并通过X射线晶体学实验验证了其结构。每个叶片由42个残基组成。携带2至10个相同叶片的蛋白质也得到了表达和纯化。两个或三个串联叶片组装在一起，重现了高度稳定的六重对称结构，这与复制和融合理论相符。其他蛋白质则产生不同的单分散复合物，大小可达42个叶片（180 kDa），它们根据简单的对称规则进行自组装。我们的方法适用于从具有所需对称性的不同蛋白质模板创建纳米构建块。
